1. Field of Invention
The present invention relates generally to apparatus and methods for inhibiting restenosis in a blood vessel after an initial treatment for opening a stenotic region in the blood vessel. More particularly, the present invention relates to radiation treatment for inhibiting hyperplasia following balloon angioplasty and other intravascular interventional treatments.
Percutaneous translumenal angioplasty (PTA) procedures are widely used for treating stenotic atherosclerotic regions of a patient""s vasculature to restore adequate blood flow. The catheter, having an expansible distal end usually in the form of an inflatable balloon, is positioned in the blood vessel at the stenotic site. The expansible end is expanded to dilate the vessel to restore adequate blood flow beyond the diseased region.
While PTA has gained wide acceptance, it continues to be limited by the frequent occurrence of restenosis. Restenosis afflicts approximately up to 50% of all angioplasty patients and is the result of injury to the blood vessel wall during the lumen opening angioplasty procedure. In some patients, the injury initiates a repair response that is characterized by smooth muscle cell proliferation referred to as hyperplasia in the region traumatized by the angioplasty. The hyperplasia of smooth muscle cells narrows the lumen that was opened by the angioplasty, thereby necessitating a repeat PTA or other procedure to alleviate the restenosis.
Many different strategies have been proposed to reduce the restenosis rate resulting from hyperplasia, including mechanical (e.g., prolonged balloon inflations during angioplasty, stenting, and the like), pharmacological, (e.g., the administration of anti-proliferative drugs following angioplasty), and other experimental procedures, all of which have had limited success.
As an alternative to mechanical devices and pharmacological drug delivery, use of intravascular radiotherapy (IRT) for the inhibition of hyperplasia following PTA has been proposed and is currently being commercialized. It has also been speculated that IRT may be used to prevent hyperplasia following cardiovascular graft procedures or other trauma to the vessel wall. Proper control of the radiation dosage is critical to impair or arrest hyperplasia without causing excessive damage to healthy tissue. Overdosing of a section of a blood vessel can cause arterial necrosis, inflammation, and hemorrhaging. Underdosing will result in no inhibition of smooth muscle cell proliferation, or even exacerbation of the hyperplasia and resulting restenosis.
A variety of catheters, guidewires, and stents have been configured for positioning a radioactive source within a blood vessel after angioplasty and other intravascular interventional treatments. In most cases, the devices have been configured to position a solid radioactive source, such as a wire, strip, pellet, or the like, within the blood vessel. It has also been proposed to deliver liquid radioactive medium to inflate a balloon catheter within the blood vessel. In the latter case, the balloon has been specially configured to prevent leakage of the radioactive material from the balloon into the blood vessel or blood stream. Of particular interest to the present invention, it has been proposed to use x-ray sources at the distal end of a catheter. The x-ray source permits convenient dosing where the source may be easily turned on and off and eliminates the need to prepare, handle, and dispose of radioisotopes.
While holding great promise, the use of radiation dosing to inhibit hyperplasia in blood vessels has not been entirely successful. In particular, hyperplasia will often still occur starting at the proximal and distal edges of an IRT treated blood vessel region and extending out 3 mm to 5 mm, producing so called xe2x80x9ccandy-wrapperxe2x80x9d ends, as illustrated in FIG. 1. It is speculated that non-uniform dose distribution at the proximal and distal edges of IRT catheters or stents is the most likely cause of this xe2x80x9ccandy-wrapperxe2x80x9d effect. In particular, it is suggested that this high rate of cell growth at the ends is due to an interaction that occurs between blood vessel tissue beyond the IRT catheter or stent edges and a low radiation dose that results from a dose fall off on the edges. Radiation dose fall off at the ends, as shown in FIG. 2, results from the fact that the total radiation experienced by any point along the length of a blood vessel will depend on the amount and distance of all radioisotope sources on either side of it. For that reason, those points near the end of the length will necessarily receive less total radiation (i.e., from all points along the treatment region) than those near the middle. As such, use of current IRT catheters or stents is problematic since it can be difficult to provide delivery of a uniform radioactive dose throughout the blood vessel wall to prevent xe2x80x9ccandy-wrapperxe2x80x9d ends.
Approaches to solving this xe2x80x9ccandy-wrapperxe2x80x9d effect are currently under investigation. Primary studies have proposed increasing the dose of radiation at the edge to push the low dose exposure to an area beyond the region of injury to the vessel wall. Although irradiating beyond the region of injury appears to be working, the major drawback of this approach is that a majority of the vessel wall ends up being irradiated, including a considerable amount of non-damaged tissue. Further, as it is believed that a vessel can not be irradiated twice since dose is cumulative, future treatment problems may arise if restenosis occurs later in already irradiated tissue. Implanting a stent with a lower activity radioisotope in the middle and higher activity radioisotopes on the ends has also been suggested. However, this approach still suffers from radiation dose fall off on tissue which are close to the blood vessel and which encourage proliferative cell growth.
For these reasons, it would be desirable to provide improved devices and methods for inhibiting restenosis and hyperplasia following angioplasty and other intravascular interventional treatments. In particular, it would be desirable to provide improved apparatus, methods, and the like, for delivering radiation dosages to the blood vessel which are sufficiently uniform to prevent hyperplasia without encountering the xe2x80x9ccandy-wrapperxe2x80x9d effect. Preferably, the improved devices and methods will be useful with all presently known modalities for delivering IRT to blood vessels including wire sources, pellet sources, liquid sources, x-ray sources, and the like. At least some of these objectives will be met by the present invention.
2. Description of the Background Art
Devices and methods for exposing intravascular and other treatment locations to radioactive materials are described in the following: U.S. Pat. Nos. 6,069,938; 5,971,909; 5,653,736; 5,643,171; 5,624,372; 5,618,266; 5,616,114; 5,540,659; 5,503,613; 5,498,227; 5,484,384; 5,411,466; 5,354,257; 5,302,168; 5,256,141; 5,213,561; 5,199,939; 5,061,267; and 5,059,166, European applications 860 180; 688 580; 633 041; and 593 136, and International Publications WO 97/07740; WO 96/14898; and WO 96/13303.
The present invention provides apparatus and methods for inhibiting hyperplasia in blood vessels after intravascular intervention. In particular, the methods can inhibit hyperplasia while reducing or eliminating the proliferative end effect, commonly called the xe2x80x9ccandy-wrapperxe2x80x9d effect, which often accompanies such treatment.
The term xe2x80x9chyperplasiaxe2x80x9d refers to the excessive growth of the vascular smooth muscle cells which can result from an injury to the blood vessel wall resulting from angioplasty or other intravascular interventional procedures. The term xe2x80x9ccandy-wrapperxe2x80x9d ends refers to a particular type of hyperplasia that often still occurs even in a radiotherapy treated blood vessel. As shown in FIG. 1, such xe2x80x9ccandy-wrapperxe2x80x9d ends typically start at the proximal and distal edges of a treatment region and extend out 3 mm to 5 mm or more. xe2x80x9cCandy-wrapperxe2x80x9d ends may result from a non-uniform radiation dose on the ends of a radiotherapy catheter or stent (see FIG. 2). Such proliferative cell growth can result in restenosis of the blood vessel lumen that was previously opened by the angioplasty even when the radiation therapy successfully inhibits hyperplasia in the center portion of the treatment region. By inhibiting hyperplasia, especially xe2x80x9ccandy-wrapperxe2x80x9d ends, the present invention can eliminate the need for subsequent angioplasty, atherectomy, bypass, and other procedures intended to restore blood perfusion.
The term xe2x80x9cintravascular interventionxe2x80x9d includes a variety of corrective procedures that may be performed to at least partially resolve a stenotic condition. The blood vessel may be any blood vessel in the patient""s vasculature, including veins, arteries, and particularly including coronary arteries, and prior to performing the initial corrective procedure, the blood vessel could have been partially or totally occluded at the target site. Usually, the corrective procedure will comprise balloon angioplasty, atherectomy, rotational atherectomy, laser angioplasty, or the like, where the lumen of the treated blood vessel is enlarged to at least partially alleviate a stenotic condition which existed prior to the treatment. The corrective procedure could also involve coronary artery bypass, vascular graft implantation, endarterectomy, or the like. Of particular interest to the present invention, the corrective procedure may additionally include procedures for controlling restenosis, such as stent placement which provides for vascular remodeling but which often does not successfully inhibit neointimal hyperplasia.
According to the present invention, a radiation delivery catheter may comprise a catheter body having a proximal end and a distal end, a pair of axially spaced apart radiation shields on the catheter body, and a radiation source. After intravascular intervention, the radiation delivery catheter is introduced percutaneously to the patient""s vasculature and advanced within the patient""s blood vessel so that the shields are positioned on either end of a treatment region. The xe2x80x9ctreatment regionxe2x80x9d will be a length within the blood vessel which is at risk of hyperplasia, typically as a result of the initial intravascular intervention(s). A radiation dose is then applied between the first and second shields so that the radiation dose directed at tissue outside of the shields is attenuated sufficiently to inhibit hyperplasia outside of the shields. Preferably, the radiation dose is radially uniform. In order to reduce the risk of hyperplasia in the treatment region between the shields, it is important to apply the radiation dose uniformly out substantially the entire distance between the spaced apart shields. In this way, the radiation can have a generally uniform dosage over the entire distance between the shields (which will preferably cover the entire region at risk of hyperplasia) while a very sharp cut off will be provided at each end of the dosed region, as defined by the shields. The sharp cut off resulting from uniform dosimetry, as seen in FIG. 3, greatly reduces the risk of xe2x80x9ccandy-wrapperxe2x80x9d ends.
The radiation shields may be permanently affixed to an outer surface of the catheter and may comprise elastomeric balloons that are filled, preferably with a non-toxic radiopaque contrast medium. The radiation shields may alternatively comprise spiral perfusion radiation balloons which allow for both perfusion and radiation blocking. Radiation shields may also be used to center and correctly position the radiation source within the blood vessel. In an exemplary embodiment, the radiation source is translated axially relative to the catheter so that the radiation source can travel between the shields to apply the uniform radiation dose. The radiation source is preferably an x-ray tube since it provides many advantages, such as being easily turned on and off, minimal disposal problems, and the like. The catheter of the present invention may also be equipped with perfusion ports proximal and distal the radiation shields to permit blood flow past the shields/balloons when inflated.
According to another embodiment of the present invention, the radiation source is a fixed source, such as a wire or liquid radioisotope filled balloon, that is immobilized on the catheter. The radiation shields are positioned immediately adjacent to each end of the fixed radioisotope source so as to inhibit hyperplasia effects at distal and proximal ends of a treatment region. The radioisotopic liquid may be selected to emit alpha, beta, or gamma radiation. Usually, alpha and beta radiation are preferred since they may be quickly absorbed by surrounding tissue and will not penetrate substantially beyond the wall of the blood vessel being treated. Accordingly, incidental irradiation of the heart and other organs adjacent to the treatment region can be substantially eliminated.
According to another embodiment of the present invention, the radiation source is a receptacle in the catheter body for receiving radioisotopic materials like pellets or liquids. In such cases, the catheter will usually include a radioisotopic inflation lumen to permit delivery and removal of the radioisotopic materials to the receptacle.
Another aspect of the present invention is a method for applying a radiation dose to a body lumen. The method includes positioning a first radiation shield at a first location in the body lumen. A second radiation shield is positioned at a second location spaced apart from the first location in the body lumen. A radially uniform radiation dose is applied between the first and second shields, so that the radiation dose directed at tissue outside of the shields is attenuated sufficiently to inhibit hyperplasia outside of the shields.